1. Technical Field of the Invention
The present invention relates to, as novel and useful industrial products, a novel class of compounds that are modulators of receptors of Peroxisome Proliferator-Activated Receptor type of subtype γ (PPARγ). This invention also relates to a process for the preparation of same and to their formulation into pharmaceutical compositions useful in human or veterinary medicine, or, alternatively, into cosmetic compositions.
2. Description of Background and/or Related and/or Prior Art
The activity of receptors of PPAR type has been the subject of many studies. See, for example, the publication entitled “Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes During the Differentiation of Human Keratinocytes”, Michel Rivier et al., J. Invest. Dermatol., 111, 1998, pp. 1116-1121, in which is listed a large number of bibliographic references relating to receptors of PPAR type. See also the report entitled “The PPARs: From orphan receptors to Drug Discovery”, Timothy M. Willson, Peter J. Brown, Daniel D. Sternbach and Brad R. Henke, J. Med. Chem., 2000, Vol. 43, pp. 527-550.
PPAR receptors activate transcription by binding to elements of DNA sequences, known as peroxisome proliferator response elements (PPRE), in the form of a heterodimer with retinoid X receptors (known as RXRs).
Three subtypes of human PPARs have been identified and described: PPARα, PPARγ and PPARδ (or NUC1).
PPARα is mainly expressed in the liver, while PPARδ is ubiquitous.
PPARγ is the most extensively studied of the three subtypes. All the references suggest a critical role of PPARγ in regulating the differentiation of adipocytes, where it is greatly expressed. It also plays a key role in systemic lipid homeostasis.
It has been described, in particular, in WO 96/33724 that PPARγ-selective compounds, such as a prostaglandin-J2 or -D2, are potential active agents for treating obesity and diabetes.
Moreover, the assignee hereof has already described PPARγ compounds and/or the use thereof in FR-2,773,075, which describes the use of PPARγ activator compounds in the preparation of a pharmaceutical composition, the composition being useful to treat skin disorders associated with an anomaly of epidermal cell differentiation.